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BLOC-ICH: Interleukin-1 Receptor Antagonist in Intracerebral Haemorrhage (BLOC-ICH)

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ClinicalTrials.gov Identifier: NCT03737344
Recruitment Status : Active, not recruiting
First Posted : November 9, 2018
Last Update Posted : March 4, 2021
Sponsor:
Collaborators:
Salford Royal NHS Foundation Trust
National Institute for Health Research, United Kingdom
Manchester University NHS Foundation Trust
Information provided by (Responsible Party):
Adrian Parry-Jones, University of Manchester

Brief Summary:

This trial will help inform the development of a new treatment for intracerebral haemorrhage (ICH; also known as haemorrhagic stroke). ICH is a type of stroke caused by spontaneous bleeding into the brain. In the hours to days after bleeding occurs, inflammation develops in the brain around the haematoma (collection of blood in the brain). Inflammation is the body's natural response to injury, however when it continues unchecked there is a risk that the brain tissue around the haematoma will become swollen. This type of swelling can worsen existing stroke symptoms or cause new deficits such as speech disturbance and limb weakness, which can lead to long term disability.

The level of inflammation in the blood is high after ICH. The investigators want to investigate whether blocking this inflammation can improve overall recovery. The investigators research group has extensively investigated the use of a well-established anti-inflammatory drug, Kineret® in trials with patients who have suffered a stroke or brain haemorrhage. Kineret® is similar to a naturally-produced protein called interleukin-1 receptor antagonist (IL-1Ra) and is already licensed to treat patients with rheumatoid arthritis. The investigators have evidence from these previous studies that Kineret® reduced levels of inflammation in the blood after ischaemic stroke (caused by a blockage in an artery). However, in order to develop Kineret® as a treatment for ICH, the investigators need to know if it reduces levels of inflammation present in the blood following ICH and if it reduces swelling in the brain.


Condition or disease Intervention/treatment Phase
Intracerebral Haemorrhage Drug: IL-1Ra Kineret® Other: IL-1Ra Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Trial of Interleukin-1 Receptor Antagonist in Intracerebral Haemorrhage: BLOcking the Cytokine IL-1 in ICH
Actual Study Start Date : May 17, 2019
Actual Primary Completion Date : February 19, 2021
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding
Drug Information available for: Anakinra

Arm Intervention/treatment
Active Comparator: IL-1Ra Kineret®
100mg doses of the trial drug Kineret® will be administered subcutaneously (SC) twice daily (12 hourly) starting within 8 hours of symptoms onset for a maximum of 3 days from symptoms onset (or sooner if discharged from neurosurgical centre).
Drug: IL-1Ra Kineret®
Kineret® 100 mg in 0.67 ml Prefilled Syringe
Other Name: Anakinra

Placebo Comparator: IL-1Ra Placebo
100mg doses of the placebo will be administered subcutaneously (SC) twice daily (12 hourly) starting within 8 hours of symptoms onset for a maximum of 3 days from symptoms onset (or sooner if discharged from neurosurgical centre).
Other: IL-1Ra Placebo
Placebo identical to Kineret® 100 mg in 0.67 ml Prefilled Syringe




Primary Outcome Measures :
  1. Oedema extension distance (OED) [ Time Frame: 72 hours (+/-12 hours) post symptoms onset ]
    Perihaematomal OED on CT scan at 72 hours (+/-12 hours), which equates to the average distance that oedema extends beyond the haematoma border.


Secondary Outcome Measures :
  1. Early haematoma growth [ Time Frame: between baseline and 72 hours post symptoms onset ]
    Early haematoma growth (defined as ≥33% or ≥6 ml increase in haematoma volume between baseline and 72 hours)

  2. Early Neurological Decline (END) [ Time Frame: between baseline and 72 hours post symptoms onset ]
    The average decrease of ≥2 in the Glasgow Coma Scale (GCS) score or an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4, lasting longer than 8 h, requiring surgical intervention, or resulting in death.

  3. Inflammatory markers [ Time Frame: from day 0 (baseline) to day 4 post randomisation ]
    Area under the curve for inflammatory markers of C-reactive protein (CRP) versus Interleukin-6 (IL-6)

  4. Quantitative blood-brain barrier permeability [ Time Frame: day 2-4 post randomisation ]
    Measure of the blood-brain barrier permeability in the perihaematomal brain using a tracer kinetic model, which generates maps of the blood-brain transfer constant K^trans

  5. modified Rankin Score (mRS) [ Time Frame: 3 months post randomisation ]
    Measure of ordinal shift in degree of disability or dependence in daily activities

  6. Stroke Impact Scale (SIS) [ Time Frame: 3 months post randomisation ]
    stroke-specific quality of life measure

  7. Fatigue severity score (FSS) [ Time Frame: 3 months post randomisation ]
    Severity of fatigue and it's effect on the participant's activities and lifestyle

  8. EQ-5D-5L [ Time Frame: 3 months post randomisation ]
    health-related quality of life measure

  9. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 3 months post randomisation ]
    Measurement of mood



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with spontaneous, non-traumatic, supratentorial ICH with no underlying macrovascular or neoplastic cause admitted to a participating centre within 8 hours of symptom onset.
  2. No concomitant health problems that, in the opinion of the principle Investigator (PI) or designee, would interfere with participation, administration of study drug or assessment of outcomes including safety.
  3. Willing and able to give informed consent or consent available from a patient representative for trial inclusion including agreement in principle to receive study drug and undergo all study assessments.
  4. Male or female aged 18 years or above.

Exclusion Criteria:

  1. Severe ICH, unlikely to survive to 72 hours scan, in the opinion of the treating clinician. For example, a GCS score < 6 at time of consent);
  2. Confirmed or suspected structural abnormality as cause of ICH (including tumour, vascular malformation).
  3. Confirmed or suspected haemorrhagic transformation of an arterial or venous infarct.
  4. Acute neurosurgery planned within 72 hours of admission.
  5. Known active tuberculosis or active hepatitis.
  6. Known active malignancy.
  7. Neutropenia (absolute neutrophil count (ANC) <1.5 x10^9/L).
  8. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) < 30 ml/minute) documented in the last 3 months prior to this ICH.
  9. Live vaccinations within the last 10 days prior to this ICH.
  10. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial.
  11. Previous or current treatment with etanercept or any other tumour necrosis factor alpha (TNFα) antagonist.
  12. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to symptom onset.
  13. Known to have participated in a clinical trial of an investigational agent or device within 5 half-lives (of the previous agent or device) prior to symptom onset.
  14. Known to be pregnant or breast-feeding or inability to reliably confirm that the patient is not pregnant.
  15. Known diagnosis of Still's disease.
  16. Clinically significant serious concurrent medical condition, premorbid illnesses, or concurrent serious infection, at the PI's (or designee's) discretion, which could affect the safety or tolerability of the intervention.
  17. Known allergy to IL-1Ra or any of the excipients listed in the drug summary of product characteristics (SmPC).
  18. Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03737344


Locations
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United Kingdom
Salford Royal NHS Foundation Trust
Manchester, North West, United Kingdom, M6 8HD
Sponsors and Collaborators
Adrian Parry-Jones
Salford Royal NHS Foundation Trust
National Institute for Health Research, United Kingdom
Manchester University NHS Foundation Trust
Investigators
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Principal Investigator: Adrian Parry-Jones, PhD, MRCP University of Manchester
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Responsible Party: Adrian Parry-Jones, NIHR Clinician Scientist & Honorary Consultant Neurologist, University of Manchester
ClinicalTrials.gov Identifier: NCT03737344    
Other Study ID Numbers: R118439
First Posted: November 9, 2018    Key Record Dates
Last Update Posted: March 4, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adrian Parry-Jones, University of Manchester:
haemorrhage
Stroke
Bleeding
Additional relevant MeSH terms:
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Cerebral Hemorrhage
Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents